Catheter systems and methods for their use in the treatment of calcified vascular occlusions

ABSTRACT

Catheter systems and methods for their use in enhancing fluid flow through a vascular site occupied by a vascular occlusion are provided. The subject catheter systems include at least an aspiration catheter and at least one of a total occlusion insert catheter and a partial occlusion insert catheter, where the insert catheters are capable of being slidably moved in the lumen of the aspiration catheter. In practicing the subject methods, a surface of the vascular occlusion is flushed with an acidic dissolution fluid using the subject catheter systems for a period of time sufficient for fluid flow through the vascular site to be enhanced, e.g. increased or established. The subject catheter systems and methods find use in the treatment of a variety of different vascular diseases characterized by the presence of calcified vascular occlusions, including peripheral and coronary vascular diseases.

TECHNICAL FIELD

[0001] The field of this invention is vascular disease, particularlyvascular diseases characterized by the presence of calcified vascularocclusions.

BACKGROUND OF THE INVENTION

[0002] Vascular occlusions, which may be partial or total occlusions,play a prominent role in many types of vascular disease. Many vascularocclusions encountered in the treatment of vascular disease arecharacterized by having a mineral component, i.e. they are calcified.Calcified vascular occlusions, both partial and total, are found in bothperipheral and coronary vascular disease

[0003] A variety of different protocols have been developed for treatingvascular diseases characterized by the presence of partial or totalocclusions. Such treatment methodologies generally involve mechanicalremoval or reduction of the size of the occlusion, and include: bypasssurgery, balloon angioplasty, mechanical debridement, atherectomy, andthe like.

[0004] Despite the plethora of different treatment strategies that havebeen developed for the treatment of vascular diseases associated withvascular occlusions, there are disadvantages associated with eachtechnique, such as tissue damage, invasiveness, etc. For example,restenosis is a common complication that results in arteries in whichocclusions have been mechanically removed.

[0005] Calcified vascular occlusions pose significant challenges tocurrently employed treatment methodologies. For example, where thetarget vascular occlusion is a total occlusion, it is difficult if notimpossible to pass a guidewire through the occlusion, which step isrequired for many of the currently used procedures. While bypass graftsare sometimes available as alternatives in such instances, bypassprocedures have their own risks and complications. Furthermore, if thereis no appropriate anastomosis site available, amputation is often theonly alternative.

[0006] As such, there is continued interest in the developmentendovascular methods of treating vascular occlusions. Of particularinterest would be the development of methods and devices suitable foruse in the treatment of calcified vascular occlusions.

[0007] Relevant Literature

[0008] U.S. patents of interest include: U.S. Pat. Nos. 4,445,892;4,573,966; 4,610,662; 4.636,195; 4,655,746; 4,690,672; 4,824,436;4,911,163; 4,976,733; 5,059,178; 5,090,960; 5,167,628; 5,195,955;5,222,941; 5,370,609; 5,380,284; 5,443,446; 5,462,529; 5,496,267 and5,785,675. See also: Koltun et al., Arch. Surg. (Aug. 1987) 122:901-905;Olin et al., Ann. Emerg. Med. (Nov. 1988) 17:1210-1215; Hargrove et al.,Surgery (December 1982) 92:981-993; and Rickard et al., CardiovascularSurg. (Dec. 1997) 5:634-640. See also PERIPHERAL ENDOVASCULARINTERVENTIONS, 2^(nd) ed. (White & Fogarty eds., Springer, N.Y.)(1996)pp 565-576.

SUMMARY OF THE INVENTION

[0009] Catheter systems and methods are provided for enhancing fluidflow, i.e. blood flow, through a vascular site occupied by a vascularocclusion. The subject catheter systems include at least an aspirationcatheter and at least one of a total occlusion insert catheter and apartial occlusion insert catheter, where the insert catheters arecapable of being slidably moved within the aspiration lumen of theaspiration catheter. In practicing the subject methods, a surface of thevascular occlusion is flushed with an acidic dissolution fluid using thesubject catheter systems for a period of time sufficient for fluid flowthrough the vascular site to be enhanced, e.g. increased or established.The subject catheter systems and methods find use in the treatment of avariety of different vascular diseases characterized by the presence ofcalcified vascular occlusions, including peripheral and coronaryvascular diseases.

BRIEF DESCRIPTION OF THE FIGURES

[0010]FIGS. 1A and 1B provide a representation of a totally occludedsuperficial femoral artery and a partially occluded superficial femoralartery, respectively.

[0011]FIGS. 2A and 2B provide representations of the aspiration catheterand the total occlusion insert catheter, respectively, while FIG. 2Cprovides a representation of the total occlusion insert catheterinserted into the lumen of the aspiration catheter to form a coaxialcatheter assembly for use in the methods of the subject invention.

[0012]FIG. 3A provides a representation of a partial occlusion insertcatheter while FIG. 3B provides a representation of the partialocclusion insert catheter inserted into the lumen of the aspirationcatheter of FIG. 2A to form a coaxial catheter assembly for use in themethods of the subject invention.

[0013]FIG. 4A provides a representation of the use of the coaxialcatheter assembly shown in FIG. 2C to flush the surface of a totalocclusion; while FIG. 4B provides a representation of the use of thecoaxial catheter assembly shown in FIG. 3B to flush the surface of apartial occlusion.

[0014]FIGS. 5A and 5B provide diagrams of systems comprising the coaxialcatheter assembly of FIG. 2C and FIG. 3B, respectively.

[0015] FIGS. 6 to 8 provide a sequential representation of the occludedvessel shown in FIG. 1 being treated according to the subject invention.

[0016]FIGS. 9 and 10 provide views of alternative embodiments of thesubject methods in which external energy is applied to the occlusion,e.g. by movement of a guidewire as shown in FIG. 9.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

[0017] Catheter systems and methods for their use to enhance fluid flowthrough a vascular site occupied by a vascular occlusion are provided.The subject catheter systems include at least an aspiration catheter andat least one of a total occlusion or partial occlusion catheter insert.In practicing the subject methods, the catheter systems are used tocontact a surface of the target vascular occlusion for a period of timesufficient to enhance, e.g. establish or improve, fluid flow through thevascular site occupied by the target occlusion. The subject systems andmethods find use in the treatment of a variety of vascular diseaseconditions characterized by the presence of vascular occlusions,including peripheral and coronary vascular disease conditions.

[0018] Before the subject invention is described further, it is to beunderstood that the invention is not limited to the particularembodiments of the invention described below, as variations of theparticular embodiments may be made and still fall within the scope ofthe appended claims. It is also to be understood that the terminologyemployed is for the purpose of describing particular embodiments, and isnot intended to be limiting. Instead, the scope of the present inventionwill be established by the appended claims.

[0019] It must be noted that as used in this specification and theappended claims, the singular forms “a,” “an,” and “the” include pluralreference unless the context clearly dictates otherwise. Unless definedotherwise all technical and scientific terms used herein have the samemeaning as commonly understood to one of ordinary skill in the art towhich this invention belongs.

[0020] Catheter Systems

[0021] As summarized above, the subject invention provides cathetersystems suitable for delivery of a fluid to a vascular site, andparticularly for delivery of an acidic dissolution fluid to a surface ofvascular occlusion. By catheter system is meant two more disparatecatheter components which are capable of being assembled into a singleunit, i.e. coaxial catheter assembly, having an inner catheter that isslidably positioned within the lumen of an outer catheter, i.e. acoaxial catheter assembly having an inner insert catheter that can bemoved relative to the outer catheter so as to produce varying distancesbetween the distal ends of the two coaxial catheters.

[0022] Aspiration Catheter

[0023] The aspiration catheter is generally an elongated tubularstructure fabricated from a flexible, biologically acceptable materialhaving a balloon or analogous vessel occlusion means positioned at itsdistal end. The length of the aspiration catheter may vary, but isgenerally from about 80 to 200 cm, usually from about 90 to 180 cm andmore usually from about 100 to 140 cm. The outer diameter of theaspiration catheter is selected so as to provide for access of thedistal end of the catheter to the vascular site via the vascular systemfrom the remote point of entry, where the outer diameter typicallyranges from about 1.0 to 4.0 mm (3 to 12 Fr), usually from about 1.5 to3.0 mm (4.5 to 9.0 Fr) and more usually from about 1.7 to 2.7 mm (5 to 8Fr). The aspiration catheter is characterized by having an open distalend, where the inner diameter at the open distal end is sufficient tohouse either a partial or total occlusion insert catheter and removefluid from the vascular site at the desired rate, e.g. a rate thatprovides for substantially isometric or isobaric pressure in thevascular site during treatment, through the resultant annular space. Theaspiration catheter at least includes an aspiration lumen. The innerdiameter of the aspiration lumen, at least at its distal end andgenerally along the entire length of the aspiration catheter, typicallyranges from about 0.2 to 2.0, usually from about 0.25 to 1.75 and moreusually from about 0.35 to 1.5 mm. Also present at the distal end of theaspiration catheter is a vessel occlusion means, where the vesselocclusion means is usually an inflatable balloon. The balloon is onethat is inflatable to a volume sufficient to substantially occlude thevessel in which the aspiration catheter is positions, e.g. by againstthe intimal surface of the vessel in which the aspiration catheter ispositioned. The balloon is in fluid or gaseous communication with aninflation lumnen that runs the length of the aspiration catheter and canbe connected to a balloon inflation means. The inflation lumen has aninner diameter that typically ranges from about 0.1 to 0.5, usually fromabout 0.2 to 0.4 mm. In certain embodiments, the aspiration catheterfurther includes a separate guidewire lumen. When present, the guidewirelumen has a diameter ranging from about 0.2 to 1.0 mm, usually fromabout 0.3 to 0.6 mm. Thus, the aspiration catheter includes at least twodistinct lumens, i.e. an aspiration lumen and a balloon inflation lumen,and in many embodiments includes three distinct lumens, i.e. anaspiration lumen, a balloon inflation lumen and a guidewire lumen.

[0024] A representation of the aspiration catheter of the subjectcatheter systems found in the subject kits is provided in FIG. 2A. InFIG. 2A, aspiration catheter 20 includes elongated tubular member 22 andballoon 24 located proximal to the distal end. The distance X betweenthe distal most portion of the balloon 24 and the distal end of thecatheter typically ranges from about 1 to 20, usually from about 5 to 10mm. Also shown is distal open end 26 through which either the partial ortotal occlusion insert catheter is moved and fluid is aspirated. Balloon24 is inflatable via balloon inflation lumen 23. Finally, device 20 isshown with optional guidewire lumen 28.

[0025] The aspiration catheter is further characterized by being capableof attaching, either directly or through one or more attachment means,at its proximal end to vacuum means, e.g. a negative pressure means,where such means is sufficient to provide for the desired aspirationduring use of the device, and a balloon inflation means, where suchmeans is sufficient to inflate the balloon at the distal end of thecatheter when desired.

[0026] Catheter Inserts

[0027] As mentioned above, the subject catheter systems also include atleast one catheter insert, where the catheter insert is capable of beingslidably positioned within the lumen of the aspiration catheter and iseither a total occlusion catheter insert or a partial occlusion catheterinsert.

[0028] The total occlusion catheter insert is an elongated tubularstructure having a blunt ended, open distal end through which fluid maybe flowed under pressure. The length of the total occlusion catheterinsert generally ranges from about 90 to 210 cm, usually from about 100to 190 cm and more usually from about 110 to 150 cm. The outer diameterof the total occlusion catheter insert is such that the catheter insertmay be slidably positioned in the lumen of the aspiration catheter, andtypically ranges from about 0.5 to 2.0, usually from about 0.8 to 1.6mm. The inner diameter of the total occlusion catheter insert typicallyranges from about 0.2 to 1.0, usually from about 0.25 to 1.0 and moreusually from about 0.3 to 1.0 mm. The total occlusion catheter insert(as well as the other catheter components of the subject cathetersystems) generally has a circular cross-sectional shape, but thecross-sectional shape could be any convenient cross-sectional shape,including avoid, irregular etc. A representation of a total occlusioncatheter insert 30 according to the subject invention is provided inFIG. 2B.

[0029] A representation of the total occlusion catheter insertpositioned inside the lumen of an aspiration catheter (i.e. as a coaxialcatheter assembly) and ready for use in the subject methods, asdescribed infra, is provided in FIG. 2C. In the coaxial catheterassembly shown in FIG. 2C, the total occlusion catheter insert and theaspiration catheter are coaxial catheters. In FIG. 2C, total occlusioncatheter insert 30 is slidably positioned in the lumen of aspirationcatheter 20. Also shown is occlusion balloon 24 which is inflated anddeflated through fluid/gaseous flow through balloon inflation lumen 23.

[0030] Alternatively or in addition to the total occlusion catheterinsert described above, the subject catheter systems may also include apartial occlusion catheter insert. The partial occlusion catheter insertdiffers from the total occlusion catheter insert in a number of ways.First, the total occlusion vascular insert includes a balloon oranalogous vessel occlusion means at its distal end. Second, the totalocclusion vascular insert has one or more fluid introduction portsproximal to the proximal side of the distal balloon. Finally, the end ofthe partial occlusion catheter insert is sealed. The length of thepartial occlusion insert generally ranges from about 90 to 250 cm,usually from about 100 to 230 cm and more usually from about 110 to 190cm. The outer diameter of the partial occlusion catheter insert is suchthat the catheter insert may be slidably positioned in the aspirationlumen of the aspiration catheter, and typically ranges from about 0.5 to2.0, usually from about 0.8 to 1.6 mm. The inner diameter of the totalocclusion catheter insert typically ranges from about 0.2 to 1.0,usually from about 0.25 to 1.0 and more usually from about 0.3 to 1.0mm.

[0031] A representative partial occlusion catheter insert is provided inFIG. 3A. In FIG. 3A, partial occlusion catheter insert 40 includeselongated tubular structure 42 that is sealed at its distal end 48.Proximal to the distal end 48 is balloon 46, where the distance Ytypically ranges from about 1 to 30 mm, usually from about 10 to 20 mm.Also depicted are infusion ports 44. The diameter of the infusion portsmay vary, but typically ranges from about 0.2 to 1.2, usually from about0.4 to 1.0 and more usually from about 0.5 to 0.8 mm. Also shown isballoon inflation lumen 43, where the balloon inflation lumen hasdimensions similar to those of balloon inflation lumen 23. As evidenced,the partial occlusion catheter insert includes two lumens, a fluidintroduction lumen and a balloon inflation lumen.

[0032]FIG. 3B shows the catheter assembly produced by insertion of thepartial occlusion catheter into the aspiration catheter. In FIG. 3B,partial occlusion catheter 40 is slidably positioned in the lumen ofaspiration catheter 20. As the two catheters are slidably positionedwith respect to one another, the distance Z between the two balloons mayvary, where during any given treatment procedure the distance Z mayrange from 1.5 to 45, usually from about 2 to 30 cm. Infusion ports 44provided for entry of a solution into the occluded space and fluid isthen aspirated through the distal end of the aspiration catheter.

[0033] The catheter inserts are further characterized by being capableof being attached at their proximal ends, either directly or through oneor more attachment means, to a fluid reservoir, e.g. an acidicdissolution fluid reservoir and, in the case of the partial occlusioncatheter insert, a balloon inflation means.

[0034] Further Catheter System Characteristics

[0035] The components of the subject catheter systems, as describedabove, may be fabricated from any convenient material, with the onlylimitation being that at least the catheter inserts and the aspirationcatheter be fabricated from a material that withstands, i.e. does notdegrade upon contact with, the acidic dissolution fluid, at least forthe period of time during which the catheter system is used. Thematerials must also be able to withstand the effects of any reactionbyproducts produced by contact of the acidic dissolution solution withthe components of the target occlusion. Suitable materials includebiocompatible polymers, e.g. polyimide, PBAX™, polyethylene, and thelike. Any glues or fittings that are employed must also be able to meetthe same criteria. Any convenient fabrication protocol may be employed,where numerous suitable protocols are known to those of skill in theart.

[0036] While the above described catheter systems have been described interms of an outer aspiration catheter and a catheter insert which servesto introduce fluid into a vascular site, i.e. as a fluid introductionmeans, during use of the subject systems (as described in greater detailbelow) these relative functions may be reversed, such that fluid isintroduced through the outer, aspiration catheter and removed throughthe catheter insert.

[0037] Methods

[0038] Also provided by the subject invention are methods of locallyintroducing active agents to vascular sites. In the broadest sense, thesubject catheter systems may be employed to introduce any active agentin a fluid delivery vehicle to a vascular site. The subject systemsachieve local delivery of active agents in fluid delivery vehicles byirrigating or flushing a portion of the vascular system with the fluidagent composition. Active agents of interest that may be locallyintroduced using the subject methods include: thrombolytic agents,growth factors, cytokines, nucleic acids (e.g. gene therapy agents).detergents and surfactants, and the like. Of particular interest is theuse of the subject catheter systems in the treatment of vascularcalcified occlusions, which application will now be described in greaterdetail as representative of the various methods in which the subjectcatheter systems may be introduced.

[0039] For treatment of vascular calcified occlusions with the subjectcatheter systems, the subject catheter systems are used to flush asurface of the target vascular occlusion with an acidic dissolutionfluid for a period of time sufficient for fluid flow to be to beenhanced through the vascular site. As indicated above, by enhanced ismeant that fluid flow is either established in situations where fluidflow is not initially present, e.g. where the target vascular occlusionis a total occlusion, or increased where some fluid flow through thevascular site is present, e.g. in situations where the vascular site isoccupied by a partial occlusion.

[0040] The Target Vascular Site

[0041] The target site through which fluid flow is enhanced by thesubject methods is a site within a vessel, typically an artery or vein,and usually an artery. In many embodiments, the vascular site is aperipheral vascular site, by which is meant that the vessel in which thevascular site is located is a vessel found in one of the extremities ofthe patient to be treated, i.e. the arms or legs. Often, the vascularsite is a site in a lower extremity vessel, e.g. a lower extremityartery. As indicated above, of particular interest are peripheralarterial vascular sites, where specific peripheral arteries of interestinclude: iliac arteries, femoropopliteal arteries, infrapoplitealarteries, femoral arteries, superficial femoral arteries, poplitealarteries, and the like. In yet other embodiments, the vascular site ispresent in a heart associated vessel, e.g. the aorta, a coronary arteryor branch vessel thereof, etc. In yet other embodiments, the vascularsite is present in a carotid artery or a branch vessel thereof.

[0042] The vascular site is occupied by a vascular occlusion in such amanner that fluid flow through the vascular site, e.g. blood flow, is atleast impeded if not substantially inhibited. By at least impeded ismeant that fluid flow is reduced by at least 20%. usually by at least50% and more usually by at least 80% through the vascular site ascompared to a control. In such situations, the vascular site is occupiedby a partial vascular calcified occlusion. By substantially inhibited ismeant that substantially no fluid flows through the vascular site. Forpurposes of this invention, fluid flow through a vascular site isconsidered to be substantially inhibited where it is not possible topass a guidewire through the vascular site, where the guidewire has adiameter ranging from 0.014 to 0.038 in and is applied to the site witha pressure ranging from about 1 to 30 oz.

[0043] A representation of a peripheral artery having a vascular siteoccupied by a total vascular calcified occlusion is provided in FIG. 1Awhile a representation of a peripheral artery having a vascular siteoccupied by a partial vascular calcified occlusion is provided in FIG.1B.

[0044] The Target Vascular Occlusion

[0045] The vascular occlusion that occupies the target vascular site isgenerally a calcified vascular occlusion, by which is meant that theocclusion includes at least some calcium containing component. Thecalcified occlusion may be a substantially pure mineral structure, ormay be a more complex formation that includes both mineral and othercomponents, including organic matter, e.g. lipids, proteins, and thelike. As mentioned above, the target vascular occlusion may be a partialor total vascular occlusion.

[0046] The mineral component making up the calcified lesion is generallymade up of one or more calcium phosphates, where the calcium phosphatesare generally apatitic. The term “apatite” as used herein refers to agroup of phosphate minerals that includes ten mineral species and hasthe general formula X₅(YO₄)₃Z, where X is usually Ca²⁺ or Pb³⁺, Y is P

or As

, and Z is F⁻, Cl⁻, or OH⁻. The term calcium apatite refers to a groupof phosphate minerals where X is Ca²⁺. The mineral component of thecalcified occlusion typically includes one or more of hydroxyapatite,carbonated hydroxyapatite (dahllite) and calcium deficienthydroxyapatite.

[0047] In addition to the mineral component, the calcified occlusionthat occupies the target vascular site may also comprise one or moreadditional components, where such components include: lipids;lipoproteins; proteins; including fibrinogen, collagen, elastin and thelike; proteoglycans, such as chondroitin sulfate, heparin sulfate,dermatans, etc.; and cells, including smooth muscle cells, epithelialcells, macrophages and lymphocytes. As such, calcified occlusions thatare targets of the subject methods include those that may be describedas: type IV, type V and type VI lesions, as defined in Stary et al.,Arterioscler. Thromb. Vasc. Biol. (1995)15:1512-1531.

[0048] In the vascular occlusions that occupy the target vascular sitesof the subject methods, the mineral component of the calcified occlusiongenerally makes up from about 10 to 100, usually from about 10 to 90 andmore usually from about 10 to 85 dry weight % of the occlusion. The sizeof the occlusion that is the target of the subject methods variesdepending on location and specific nature of the occlusion. Generally,the volume of the occlusion will range from about 20 to 10,000 mm³,usually from about 30 to 500 mm³ and more usually from about 50 to 300mm³.

[0049] In certain embodiments, one or both ends of the occlusion may becharacterized by being primarily thrombotic material, e.g. a thrombus,where the thrombotic domain of the occlusion extends for about 1 to 5cm. The nature of the thrombotic domain may be organized ordisorganized.

[0050] Contacting the Vascular Occlusion with an Acidic DissolutionFluid

[0051] In the subject methods, one surface of the vascular occlusion,either the distal or proximal surface, is contacted with an acidicdissolution fluid for a period of time sufficient for fluid flow to beestablished through the vascular site. Contact with the vascular sitemay be accomplished in any convenient manner, so long as it results inthe enhancement of fluid flow through the vascular site. Generally, thesurface is dynamically contacted or flushed with the acidic dissolutionfluid.

[0052] By dynamic contact is meant that the fresh dissolution solutionis contacted with the surface of the target occlusion one or more times,including continuously. during the treatment period. In many preferredembodiments of the subject methods, the surface of the target occlusionis continuously contacted or flushed with the acidic dissolution fluid.In other words, the acidic dissolution fluid is introduced in a mannersuch that a continuous flow of the acidic dissolution fluid across thesurface of the occlusion is achieved.

[0053] Where the surface of the target occlusion is flushed with thedissolution fluid, it is preferred that the pressure in the localenvironment which includes the surface of the occlusion, i.e. the areabounded by the vessel walls, the surface of the target occlusion and thecatheter system used to delivery the solution, remains substantiallyisometric. By substantially isometric is meant that the pressure in thelocal environment does not vary by a significant amount, where theamount of variance over the treatment period does not vary by more thanabout 50%, usually by not more than about 10% and more usually by notmore than about 5%. In other words, the local environment remainssubstantially isobaric during the treatment period. Accordingly, wherefluid is dynamically contacted with the surface of the target occlusion,fluid is also simultaneously removed from the local environmentcomprising the surface of the target occlusion, such that the overallvolume of fluid in the local environment remains substantially constant,where any difference in volume at any two given times during thetreatment period does not exceed about 50%, and usually does not exceedabout 10%. As such, the dissolution fluid is introduced into the localenvironment of the target lesion in a manner such that the localenvironment remains substantially isovolumetric.

[0054] Where the acidic dissolution fluid is dynamically introduced intothe vascular site, the dissolution fluid is introduced in a manner suchthat the flow rate of the dissolution through the vascular site of thelesion is generally at least about 10 cc/min, usually at least about 20cc/min and more usually at least about 60 cc/min, where the flow ratemay be as great as 120 cc/min or greater, but usually does not exceedabout 1000 cc/minute and more usually does not exceed about 500cc/minute, where by “volume” is meant the local environment of theocclusion, as defined above. The total amount of dissolution fluid thatis passed through the local environment of the lesion during thetreatment period typically ranges from about 100 to 1000 cc, usuallyfrom about 200 to 800 cc and more usually from about 400 to 500 cc. Thesolution is generally pressurized to achieve the desired flow rate, asdescribed stipra. As such, the pressure at the distal end of the coaxialcatheter assembly through which the solution is introduced into thelocal environment typically ranges from about 50 to 1200 psi, usuallyfrom about 100 to 600 psi and more usually from about 200 to 400 psi. Itis important to note that the overall pressure in the local environmentis maintained at substantially isometric or isobaric conditions. Assuch, the negative pressure at the entrance to the aspiration catheter,e.g. the open annulus at the distal end of the aspiration catheter willbe of sufficient magnitude to provide for substantially-isobaricconditions. Preferably, the overall pressure in the local environment ismaintained at a value ranging from about 0.1 to 3 psi, usually fromabout 0.5 to 2.5 psi and more usually from about 1 to 2 psi.

[0055] The methods by which the subject catheter systems described aboveare employed to flush a surface of the target occlusion with the acidicdissolution solution are now further discussed in terms of FIGS. 4A and4B. FIG. 4A provides a representation of a catheter assembly accordingto the subject invention flushing a total occlusion in an artery 36. InFIG. 4A, artery 36 is totally occluded by calcified vascular occlusion32. Coaxial catheter assembly made up of total occlusion catheter insert30 inside of aspiration catheter 20 is positioned proximal to onesurface of occlusion 32, e.g. by advancement over a guidewire withimaging, as described in the experimental section infra. Next, acidicdissolution fluid is introduced through the distal open end of catheter30, whereby it contacts the proximal surface of the occlusion 32.Simultaneously, fluid is removed from the local environment 38 throughthe annular space formed at the distal open end 26 of the aspirationcatheter 20. The local environment is isolated from the remainder of thehost's circulatory system by inflated balloon 24.

[0056]FIG. 4B provides a representation of contacting the surface of apartial vascular occlusion using the subject catheter systems. In FIG.4B, the coaxial catheter assembly that includes partial occlusioncatheter insert 46 and aspiration catheter 20 is positioned in thevascular site, e.g. with the aid of a guidewire and imaging, such thatthe distal end 48 and balloon 46 of the catheter insert are on one sideof partial occlusion 34 and the distal end 26 and balloon 24 ofaspiration catheter 20 are on the other side of partial occlusion 34.Fluid is then introduced into the local environment (i.e. the spacebordered by the arterial walls and the two balloons) through infusionports 44. Simultaneously, fluid is removed through the annular spacepresent at the distal end 26 of aspiration catheter 20, as indicated bythe arrows.

[0057] Time Period

[0058] The surface of the target occlusion is contacted, e.g. flushed,with the acidic dissolution fluid for a period of time sufficient forfluid flow to be enhanced through the vascular site, e.g. established orimproved. As such, where the target occlusion is a total occlusion,contact is maintained for a period of time sufficient for a guidewire tobe passed through the vascular site, as described above. Alternatively,where the target occlusion is a partial occlusion, contact is achievedfor a period of time sufficient for the rate of fluid flow to beincreased through the vascular site, generally by at least about 10%,usually by at least about 50%, and in many embodiments by at least about100%. Generally, the period of time during which the surface of theocclusion is contacted with the acidic dissolution solution ranges fromabout 5 to 100 minutes, usually from about 10 to 30 minutes. Wherecontact is achieved by flushing the target occlusion with the acidicdissolution solution, the contact duration typically lasts for a periodof time ranging from about 5 to 30 minutes, usually from about 10 to 30minutes and more usually from about 10 to 20 minutes.

[0059] Acidic Dissolution Solutions

[0060] A variety of different types of acidic dissolution solutions maybe employed in the subject methods. The acidic treatment solutions thatfind use in the subject methods generally have a pH of less than about6.5, where the pH is usually less than about 4.0 and more usually lessthan about 3.0. In many preferred embodiments, the pH ranges from 0 to2, and usually 0 to 1. The acidic treatment solution can include anumber of different types of acids, where the acids may or may notinclude a hydrocarbon moiety, i.e. a hydrogen bonded directly to acarbon atom. Suitable acids that lack a hydrocarbon moiety includehalogen acids, oxy acids and mixtures thereof, where specific acids ofinterest of this type include, but are not limited to, hydrochloric,nitric, sulfuric, phosphoric, hydroboric, hydrobromic, carbonic andhydroiotic acids. For such acids, the acid can be a concentrated acid,or can be diluted. Upon dilution, the concentration of an inorganic acidwill generally be from about 10 N to about 0.01 N, preferably between 5N to 0.1 N. Also of interest are acids that include a hydrocarbonmoiety, where such acids include, but are not limited to, any organicacid of one to six (C₁ to C₆) carbons in length. Organic acids of thistype include, but are not limited to, formic, acetic, propionic, maleic,butanoic, valeric, hexanoic, phenolic, cyclopentanecarboxylic, benzoic,and the like. For an organic acid, thacicid can be in concentrated form,or can be diluted. The acidic treatment solution can be composed ofeither a monobasic or a polybasic acid. Acids are “monobasic” when theyhave only one replaceable hydrogen atom and yield only one series ofsalts (e.g., HCl). Acids are “polybasic” when they contain two or morehydrogen atoms which may be neutralized by alkalies and replaced byorganic radicals.

[0061] In many embodiments of the subject invention, the acid solutionis hypertonic, by which is meant that the osmolarity of the solution isgreater than that of a red blood cell, i.e. the osomolarity is greaterthan 300 mosmol. The solution may be rendered hypertonic by includingany convenient component or components in the solution which provide forthe desired elevated osmolarity.

[0062] Any convenient agent that is capable of increasing the osmolarityof the solution may be employed, where suitable agents include salts,sugars, and the like. In many embodiments, the agent that is employed torender the solution hypertonic is one or more, usually no more thanthree, and more usually no more than two, different salts. Generally,the salt concentration in these embodiments of the solution is at leastabout 100 mosmol, usually at least about 200 mosmol and more usually atleast about 300 mosmol, where the concentration may be as high as 3000mosmol or higher, depending on the particular salt being employed torender the solution hypertonic, where the solution may be saturated withrespect to the salt in certain embodiments. Salts that may be present inthe subject solutions include: NaCl, MgCl₂, Ringers, etc. where NaCl ispreferred in many embodiments.

[0063] Hydrogen Chloride Solutions

[0064] Of particular interest in many embodiments is the use of ahydrogen chloride solution. In hydrogen chloride solutions that find usein the subject invention, the concentration of HCl in the solutionranges from about 0.001 to 1.0 N, usually from about 0.01 to 1.0 N andmore usually from about 0.1 to 1.0 N. In many embodiments, the hydrogenchloride solution will further include one or more salts which make thesolution hypertonic, as described above. In certain preferredembodiments, the salt is NaCl, where the concentration of NaCl in thesolution is at least 0.05 M, usually at least 0.10 M, and more usuallyat least 0.15 M, where the concentration may be as high as 0.25 M orhigher. In certain embodiments, the solution will be saturated withNaCl.

[0065] Of particular interest are aqueous hydrogen chloride solutionsthat consist of water, hydrogen chloride and NaCl. The concentration ofhydrogen chloride in these solutions of particular interest ranges fromabout 0.01 to 1.0 N, usually from about 0.05 to 0.5 N and more usuallyfrom about 0.075 to 0.25 N. The concentration of NaCl in these solutionsof particular interest ranges from about 0.05 to 0.25 M, usually fromabout 0.05 to 0.10 M

[0066] Further Embodiments of the Subject Methods

[0067] In a number of embodiments of the subject methods, the methods inwhich the surface of the target occlusion is contacted with an acidicdissolution fluid may be modified to include a number of additionalmethod steps. Additional method steps that may be present in the overallprocess include: rendering the local environment of the target occlusionbloodless, contacting the target occlusion with a solution designed toremove organic components, washing or rinsing the local environment ofthe target occlusion, applying external energy to the target occlusion;imaging the target vascular site; establishing or expanding a passagewaythrough an initial thrombotic domain of the target occlusion; and thelike.

[0068] Rendering the Local Environment Bloodless

[0069] In many preferred embodiments, as described above, the localenvironment of the target occlusion is rendered substantially bloodlessprior to introduction of the dissolution fluid. In these embodiments,the balloon(s) of the assembled catheter system is inflated tophysically isolated the local environment from the remainder of thecirculatory system and then the local environment is flushed with aphysiologically acceptable solution, such that substantially all of theblood present in the solution is removed. Typically, a washing solutionwill be employed in this step of rendering the local environmentbloodless. Examples of washing solutions that may find use in theseembodiments include: water for injection, saline solutions, e.g.Ringer's, phosphate buffered saline, or other physiologically acceptablesolutions. The washing solution includes an anticlotting factor in manyembodiments, where anticlotting factors of interest include heparin andthe like. The washing solution can also contain chelating agents.

[0070] Use of Organic Structure Dissolution Solutions

[0071] As mentioned above, in addition to the acidic dissolutionsolution, certain embodiments of the subject invention include a step ofcontacting the target occlusion with a dissolution solution which servesto remove at least a portion of the non-mineral, typically organic,phase of the target occlusion. The nature of this “organic phasedissolution solution” varies depending on the nature of the targetocclusion. Representative active agents that may be present in thisorganic phase dissolution solution include: oxidizing agents; organicsolvents; lipid dissolving agents such as surfactants, e.g. TWEEN™, anddetergents, where ionic detergents are of particular interest, e.g.cholic acid, glycocholic acid, benzylkonium chloride; enzymes, and thelike.

[0072] Application of External Energy

[0073] In certain embodiments, external energy is applied to thevascular site to promote mechanical break-up of the occlusion intoparticles or debris that can be easily removed from the vascular site.Any means of applying external energy to the vascular site may beemployed. As such, jets or other such means on a catheter device whichare capable of providing varying external forces to the occlusionsufficient to cause the occlusion to break up or disrupt may beemployed. Of particular interest in many embodiments is the use ofultrasound. The ultrasound can be applied during the entire time ofcontact of the cardiovascular tissue with the acidic treatment solution,or the ultrasound can be applied for only part of the treatment period.In one embodiment, ultrasound is applied for several short periods oftime while the dissolution treatment solution is contacted with thetarget occlusion. There are several devices for the application ofultrasound to cardiovascular tissue known to those of skill in the art.See e.g. U.S. Pat. No. 4,808,153 and U.S. Pat. No. 5,432,663, thedisclosures of which are herein incorporated by reference.

[0074] In such methods where external energy is applied to the occlusionin order to disrupt or break-up the occlusion into particles or debris,the particles or debris may range in size from about 0.01 to 4.0 mm,usually from about 0.1 to 2.0 mm and more usually from about 0.5 to 1.0mm. In such instances, the method may further include a step in whichthe resultant particles are removed from the vascular site. Particlesmay be removed from the vascular site using any convenient means, suchas the catheter of the subject invention described in greater detailinfra.

[0075] Another means that may be employed to apply external energy tothe lesion during the dissolution process is to use a mechanical meansof applying external energy. Mechanical means of interest include movingstructures, e.g. rotating wires, guidewires, which physically contactthe target occlusion and thereby apply physical external energy to thetarget lesion.

[0076] Imaging

[0077] In addition, it may be convenient to monitor or visualize thevascular site prior to or during treatment. A variety of suitablemonitoring means are known to those of skill in the art. Any convenientmeans of invasive or noninvasive detection and/or quantification may beemployed. Such means include plain film roentgenography, coronaryarteriography, fluoroscopy, including digital subtraction fluoroscopy,cinefluorography, conventional, helical and electron beam computedtomography, intravascular ultrasound (IVUS), magnetic resonance imaging,transthoracic and transesophageal echocardiography, rapid CT scanning,antioscopy and the like. Any of these means can be used to monitor thevascular site before, during or after contact with the dissolutionfluid.

[0078] In many embodiments, an imaging agent is employed, where theimaging agent may or may not be present in the acidic dissolutionsolution. Imaging agents of particular interest include: non-ionicimaging agents, e.g. CONRAY™, OXILAN™, and the like.

[0079] Thrombus Removal Step

[0080] The subject methods may further include a thrombus removal step,e.g. where the calcified domain of the target occlusion is covered by athrombotic domain, as described above. In such methods, any thrombusremoval means that is capable or providing suffcient access of theacidic dissolution solution to the surface the calcified domain of thetarget lesion may be employed. Thus, where the thrombotic domain is adisorganized domain, it may be sufficient to pass increasingly largerdiameter guidewires through the domain until a passageway of sufficientwidth to provide access of the catheter assembly described above to thesurface of the occlusion is established. Alternatively, portions of thethrombotic domain may be removed, e.g. via atherectomy methods,angioplasty methods, and the like, where devices for performing suchprocedures are known to those of skill in the art. See the patentreferences cited in the Relevant Literature section, supra, whichreferences are herein incorporated by reference.

[0081] Use of a Plurality of Solutions

[0082] In many embodiments, the subject methods include contacting thesurface of the target occlusion with a plurality, i.e. two or more,distinct solutions, one of which is an acidic dissolution solution.Where one or more additional distinct solutions, such as primingsolutions, washing solutions, organic phase dissolution solutions andthe like are employed, as described below, such disparate solutions aregenerally introduced sequentially to the vascular site. For example, thetarget occlusion may be contacted with the following order of solutions:(1) washing solution to render the local environment substantiallybloodless; (2) organic phase dissolution solution, e.g. detergentsolution such as cholic acid solution, to remove organic phases from thetarget lesion; (3) acidic dissolution solution to demineralize thetarget occlusion; and (4) washing solution. Other sequences of solutionapplication can also be employed. See U.S. patent application Ser. No.09/353,127, the disclosure of which is herein incorporated by reference.

[0083] Outcome

[0084] As discussed above, the subject methods result in the enhancementof fluid flow through the vascular site occupied by the occlusion. Fluidflow is considered to be enhanced in those situations where the vascularsite is totally occluded when a guide wire can be moved through thevascular site without significant resistance. Fluid flow is consideredto be enhanced in those situations in which the vascular site ispartially occluded when the rate of fluid flow through the vascular siteincreases by at least 10%, usually by at least 50% and in manyembodiments by at least 100%.

[0085] In certain embodiments, the subject methods will not result incomplete removal of the target occlusion from the vascular site. Assuch, the vascular site, while not totally occluded, may still includelesion deposits on the wall which impede fluid flow through the vascularsite and the removal or reduction of which is desired. Any convenientprotocol for treating these remaining deposits may be employed, e.g.balloon angioplasty, atherectomy, stenting, etc. Also of interest is theuse of two balloon catheters and an acidic dissolution solution, asdescribed in PCT/US99/15918, the disclosure of which is hereinincorporated by reference.

[0086] Of particular interest in those embodiments where the vascularsite is initially totally occluded, fluid flow through the totalocclusion is first established using the catheter assembly made up ofthe total occlusion catheter insert inside the aspiration catheter.Following establishment of fluid flow, the rate of fluid flow isincreased using the catheter assembly made up of the partial occlusioncatheter insert inside the aspiration catheter.

[0087] Systems

[0088] Also provided by the subject invention are systems for practicingthe subject methods, i.e. for enhancing fluid flow through a vascularsite occupied by a vascular occlusion. The subject systems at leastinclude the catheter systems as described above, a manifold, a fluidreservoir for storing acidic dissolution fluid and a negative pressuremeans for providing aspiration or suction during use of the system. Thesystems may further include a number of optional components, e.g.guidewires, pumps for pressurizing the dissolution fluid, and the like.

[0089] In the system depicted in FIG. 5A, system 50 includes catheterassembly 51, manifold 52 with three entry ports (52 a, 52 b and 52 c),acidic dissolution fluid reservoir 53, negative pressure means 54 andballoon inflation means 55. Catheter assembly 51 is as described in FIG.2C, having aspiration catheter 20 encompassing total occlusion catheterinsert 30. Balloon 24 is positioned on the aspiration catheter at alocation proximal to the distal end of the aspiration catheter. Manifold52 has three ports, 52 a, 52 b and 52 c. Port 52 a serves as the balloonport, and is attached to a balloon inflation means 55, e.g. a syringe,during use. The syringe 55 is in fluid or gaseous communication with theinterior of balloon 24 through a lumen that extends the length of theaspiration catheter (not shown). Port 52 b serves as the guidewire portand injection port, and is attached in fluid communication to acidicdissolution fluid reservoir 53 during use. In certain embodiments, apumping means (not shown) may be present to provide for desired pressureof the acidic dissolution fluid into the fluid introduction means andout of the distal end of the catheter device 51. Port 52 c serves as theaspiration port through which fluid travels from the vascular sitethrough the catheter device 51 and out of the patient. Port 52 c isconnected to negative pressure means 54 and optionally fluid outflowreservoir (not shown).

[0090] The system shown in FIG. 5A is one which is ready for use in thetreatment of a total vascular occlusion, as described above. In thoseembodiments where one wishes to treat a partial vascular occlusion usinga catheter assembly having a partial occlusion catheter insert inside anaspiration catheter, as shown in FIG. 3B and 4B, an analogous system asdepicted in FIG. 5B is employed. The system depicted in FIG. 5B isanalogous to that shown in FIG. 5A. In the assembly shown if FIG. 5B,manifold 52 in an expanded manifold that includes additional port 56 forsecond balloon inflation means 57.

[0091] Utility

[0092] The subject devices and methods find use in a variety ofdifferent applications in which it is desired to enhance fluid flow,usually blood flow, (or at least pass a guidewire through), a vascularsite that is occupied by a calcified vascular occlusion, e.g. a partialor total occlusion. As such, the subject methods and devices find use inthe treatment of peripheral vascular disease, etc. The subject methodsalso find use in the treatment of coronary vascular diseases. Bytreatment is meant that a guidewire can at least be passed through thevascular site under conditions which, prior to treatment, it could not.Treatment also includes situations where the subject methods provide forlarger fluid passageways through the vascular site, including thosesituations where fluid flow is returned to substantially the normal ratethrough the vascular site. The subject methods may be used inconjunction with other methods, including balloon angioplasty,atherectomy, and the like, as part of a total treatment protocol.

[0093] A variety of hosts are treatable according to the subjectmethods. Generally such hosts are “mammals” or “mammalian,” where theseterms are used broadly to describe organisms which are within the classmammalia, including the orders carnivore (e.g., dogs and cats), rodentia(e.g., mice, guinea pigs, and rats), lagomorpha (e.g. rabbits) andprimates (e.g., humans, chimpanzees, and monkeys). In many embodiments,the hosts will be humans.

[0094] Kits

[0095] Also provided by the subject invention are kits for use inenhancing fluid flow through a vascular site occupied by an occlusion.The subject kits at least include a catheter system, as described above,where the catheter system at least includes an aspiration catheter andone of, usually both of, a partial occlusion catheter insert and a totalocclusion catheter insert. The kits may further include one or moreadditional components and accessories for use with the subject cathetersystems, including tubing for connecting the various catheter componentswith fluid reservoirs, syringes, pumping means, etc., connectors, one ormore guidewires, dilators, vacuum regulators, etc.

[0096] In certain embodiments, the kits further include one or moresolutions, or precursors thereof, where in such embodiments the kits atleast include an acidic dissolution fluid, such as a hydrochloric acidsolution, as described above, where the solution may be present in acontainer(s), e.g. a flexible bag, a rigid bottle, etc. For kits thatare to be used in methodologies in which the fluid is flushed throughthe local environment of the lesion, the amount of dissolution fluidpresent in the kit ranges from about 1 to 500 liters, usually from about10 to 200 liters and more usually from about 50 to 100 liters.Alternatively, the kit may comprise precursors of the dissolutionsolution for use in preparing the solution at the time of use. Forexample, the precursors may be provided in dry form for mixing with afluid, e.g. water, at the time of use. In addition to the dissolutionfluid or precursors thereof, the kit may further comprise one or moreadditional fluids (or dry precursors thereof), such as a primingsolution, a washing solution, contrast medium, and the like.

[0097] Other elements that may be present in the subject kits includevarious components of the systems, including manifolds, ballooninflation means, e.g. syringes, pumping means, negative pressure meansetc.

[0098] Finally, the kits will include instructions for practicing thesubject methods, where such instructions may be present on one or moreof the kit components, the kit packaging and/or a kit package insert.

[0099] The following examples are offered by way of illustration and notby way of limitation.

Experimental

[0100] I. A 50 year old male having a total occlusion in the superficialfemoral artery (SFA) as shown in FIG. 1 is treated as follows. In FIG.1, the external iliac artery is shown as it branches into the SFA 12 andthe profunda 13. Also shown are the medial circumflex and the latercircumflex, 14 and 15 respectively. The SFA is totally occluded byocclusion 16.

[0101] 1. The patient is heparinized using standard procedures.

[0102] 2. An introducer sheath is placed either in the same leg toprovide retrograde access or in the opposite leg to provide cross-overaccess.

[0103] 3. A guidewire is inserted and advanced to the site of the totalocclusion.

[0104] 4. The catheter system as shown in FIG. 5A is employed asfollows. The catheter device is inserted so that the distal end of thedevice is at the vascular site occupied by the total occlusion, as shownin FIG. 6. The balloon 24 is then inflated by depressing the syringe 55,such that the balloon occludes the vessel proximal to the occlusion, asshown in FIG. 6. The local environment 60 bordered by the proximalsurface of the occlusion, the SFA vessel walls and the distal surface ofthe inflated balloon 24 is indicated by dashed lines.

[0105] 5. Contrast medium is then injected into the vascular sitethrough port 52 b to confirm the location of the distal end of thecatheter and the inflated balloon.

[0106] 6. A sufficient amount of heparinized phosphate buffered salineis then injected through port 52 b into the isolated vascular site orlocal environment 60 and aspirated therefrom such that the isolatedlocal environment 60 is rendered substantially bloodless.

[0107] 7. The surface of the total occlusion is then flushed with acidicdissolution fluid A (0.1N HCl, 0.05 M NaCl) by introducing solution Athrough port 52 b into the vascular space and removing or aspiratingfluid from the vascular site through port 52 c, as shown in FIG. 6. Seealso FIG. 4A.

[0108] 8. As the occlusion is demineralized, the central fluidintroduction catheter 30 is advanced independent of the aspirationcatheter/outer catheter 20, as shown in FIG. 7.

[0109] 9. Where desired, balloon 24 may be deflated, aspiration catheter20 repositioned, and then balloon 24 may be reinflated to move thedistal end of the total occlusion catheter insert 30 to a site furtherinto the occlusion 17, as shown in FIG. 8.

[0110] 10. Once a passage through the occlusion sufficient to pass aguidewire through the occlusion is produced, the device is removed.

[0111] 11. The above procedure results in fluid flow through thevascular site occupied by the lesion being reestablished, as evidencedby passing a guidewire through the vascular site.

[0112] 12. Where desired, following reestablishment of fluid flowthrough the total occlusion, the total occlusion catheter insert isremoved. A guidewire is then inserted through the large lumen ofaspiration catheter 20 to a space beyond the distal end of theocclusion. A partial occlusion catheter insert is then introduced overthe guidewire to a position such that the balloon at the distal end ofthe insert is on the far side of the partial occlusion.

[0113] 13. A system as shown in FIG. 5B is then employed to inflate theballoon of the insert, establish a bloodless local environment and flushthe remaining partial occlusion with acidic dissolution fluid, as shownin FIG. 4B.

[0114] II. Variations on the Above Procedure

[0115] The above procedure is performed with the additional step ofapplying mechanical energy to the occlusion during flushing with theacidic dissolution solution. FIG. 9 shows mechanical energy beingapplied to the occlusion by contacting a guidewire 91 with the surfaceof the total occlusion during flushing. FIG. 10 shows mechanical energybeing applied to the surface of the occlusion with the proximal end ofthe total occlusion insert. Other means of applying external energy,e.g. mechanical energy, may also be employed.

[0116] It is evident from the above discussion and results that improvedmethods of enhancing blood flow through a vascular occlusion areprovided. Specifically, the subject invention provides a means forreadily establishing fluid flow through a vascular site totally occludedby a calcified vascular occlusion, which has heretofore been difficultto practice. As such, the subject invention provides a means for usingless traumatic procedures for treating peripheral vascular disease,thereby delaying or removing the need for graft procedures and/oramputation. As such, the subject invention represents a significantcontribution to the field.

[0117] All publications and patent applications cited in thisspecification are herein incorporated by reference as if each individualpublication or patent application were specifically and individuallyindicated to be incorporated by reference. The citation of anypublication is for its disclosure prior to the filing date and shouldnot be construed as an admission that the present invention is notentitled to antedate such publication by virtue of prior invention.

[0118] Although the foregoing invention has been described in somedetail by way of illustration and example for purposes of clarity ofunderstanding, it is readily apparent to those of ordinary skill in theart in light of the teachings of this invention that certain changes andmodifications may be made thereto without departing from the spirit orscope of the appended claims.

What is claimed is:
 1. A catheter system comprising: (a) an aspirationcatheter comprising an elongated tube having an aspiration lumen endingin an open distal end and an inflatable balloon at said distal end; and(b) at least one of: (i) a total occlusion catheter insert comprising anelongated tube having an open distal end; and (ii) a partial occlusioncatheter insert comprising an elongated tube having a sealed distal end,an inflatable balloon at said distal end and at least one infusion portproximal to said inflatable balloon wherein said total and partialocclusion catheter inserts are capable of being slidably positionedwithin said aspiration catheter to produce an annular space at thedistal end of said aspiration catheter through which fluid may flow. 2.The catheter system according to claim 1, wherein said system comprisesboth said partial and total occlusion catheter insert.
 3. The cathetersystem according to claim 1, wherein said aspiration catheter furthercomprises a guidewire lumen separate from said aspiration lumen.
 4. Acoaxial catheter assembly comprising: (a) an aspiration cathetercomprising an elongated tube having an aspiration lumen ending in anopen distal end and an inflatable balloon at said distal end; and (b)one of: (i) a total occlusion catheter insert comprising an elongatedtube having an open distal end; or (ii) a partial occlusion catheterinsert comprising an elongated tube having a sealed distal end, aninflatable balloon at said distal end and at least one infusion portproximal to said inflatable balloon slidably positioned within saidaspiration lumen of said aspiration catheter in a manner such that anannular space through which fluid may flow is present at the distal endof said aspiration catheter.
 5. The coaxial catheter assembly accordingto claim 4, wherein said total occlusion catheter insert is slidablypositioned within said aspiration lumen.
 6. The coaxial catheterassembly according to claim 4, wherein said partial occlusion catheteris slidably positioned within said aspiration lumen.
 7. A method ofenhancing fluid flow through a vascular site occupied by a vascularocclusion, said method comprising: flushing a surface of said vascularocclusion with an acidic dissolution fluid for a period of timesufficient for fluid flow to be enhanced through said vascular site;whereby fluid flow is established through said vascular site.
 8. Themethod according to claim 7, wherein said vascular occlusion comprisescalcium.
 9. The method according to claim 7, wherein said occlusion is atotal occlusion.
 10. The method according to claim 7, wherein saidocclusion is a partial occlusion.
 11. The method according to claim 7,wherein a coaxial catheter assembly according to claim 4 is used toflush said surface of said vascular occlusion.
 12. The method accordingto claim 11, wherein said coaxial catheter assembly is the assemblyaccording, to claim
 5. 13. The method according to claim 11, whereinsaid coaxial catheter assembly is the assembly according to claim
 6. 14.A method of flushing a vascular site with a solution, said methodcomprising: introducing and removing said solution from said vascularsite with a coaxial catheter assembly according to claim
 4. 15. Themethod according to claim 14, wherein said coaxial catheter assembly isthe assembly according to claim
 5. 16. The method according to claim 14,wherein said coaxial catheter assembly is the assembly according toclaim
 6. 17. A system for enhancing fluid flow through a vascular siteoccupied by a vascular occlusion, said system comprising: (a) a coaxialcatheter assembly according to claim 4; (b) a manifold; (c) an acidicfluid dissolution reservoir in fluid communication the insert catheterof said coaxial catheter assembly; and (d) a source of negative pressurein fluid communication with said aspiration lumen of said coaxialcatheter assembly.
 18. The system according to claim 17, wherein saidsystem further includes a balloon inflation means.
 19. The systemaccording to claim 18, wherein said balloon inflation means is asyringe.
 20. The system according to claim 17, wherein said systemfurther comprises a guidewire.
 21. A kit for use in enhancing fluid flowthrough a vascular site occupied by a vascular occlusion, said kitcomprising: a catheter system according to claim
 1. 22. The kitaccording to claim 21, wherein said kit further comprises a guidewire.23. The kit according to claim 21, wherein said kit further comprises animaging agent.
 24. The kit according to claim 21, wherein said kitfurther comprises an acidic dissolution solution.
 25. A kit for use inenhancing fluid flow through a vascular site occupied by a vascularocclusion, said kit comprising: (a) a catheter system according to claim1; (b) an acidic dissolution solution; and (c) a guidewire.
 26. The kitaccording to claim 25, wherein said kit further comprises a washingsolution.
 27. The kit according to claim 25, wherein said kit furthercomprises a surfactant solution.
 28. The kit according to claim 25,wherein said kit further comprises an imaging agent.
 29. An acidicdissolution fluid consisting essentially of: hydrogen chloride in aconcentration ranging from about 0.01 to 1.0 N; and water.
 30. Thesolution according to claim 29, wherein said solution further consistsof a salt.
 31. The solution according to claim 30, wherein said salt isNaCl.
 32. The solution according to claim 31, wherein said NaCl ispresent in a concentration ranging from about 0.01 to 0.1 M.